This dissertation addresses some fundamental aspects of mechanical stimulation of the chondrocytes within the growth plate. The motivation of these studies is to better understand the mechanical mechanisms involved in the autoregulation and functional adaptation of soft tissues. The ultimate goal of this basic science research is to provide a basis for tissue modulation and tissue engineering through mechanical stimulation and manipulation.
The intrinsic biphasic material properties of live growth plate tissue were determined from in vitro experiments on growth plate explants in a bovine animal model. The cellularity of the growth plate was then used to investigate the mechanical coupling of the chondrocytes with their extracellular matrix. Specifically, the mechanical contribution of the chondrocytes' cytoskeleton was established by testing explants after inhibiting the polymerization of the actin filament network with cytochalasin-D.
A new quantitative technique utilizing laser scanning optical microscopy was developed for determining the deformation of living cells in growth plate as the tissue is deformed. A study monitoring the deformation of growth plate chondrocytes in situ provided information regarding the relative mechanical properties of the chondrocytes in the different histological zones of the growth plate and their surrounding extracellular matrix.
Finally, a model was developed in order to determine the mechanical environment of cells within hydrated soft tissues. The model treats the chondrocytes as mechanical inclusions within the extracellular matrix with the cell and extracellular matrix modeled as biphasic materials with distinct material properties. The solution was applied to confined compression, a standard explant loading configuration. Specific mechanical perturbations that may be involved in the process of mechanical signal transduction were addressed (e.g, flow fields, membrane stretch, pressure and volume change)
|1957||Eshelby JD. The determination of the elastic field of an ellipsoidal inclusion, and related problems. Proc R Soc Lon Ser-A. 1957;241(1226):376-396.|
|1989||Mow VC, Gibbs MC, Lai WM, Zhu WB, Athanasiou KA. Biphasic indentation of articular cartilage, II: a numerical algorithm and an experimental study. J Biomech. 1989;22:853-861.|
|1991||Athanasiou KA, Rosenwasser MP, Buckwalter JA, Malinin TI, Mow VC. Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. J Orthop Res. May 1991;9(3):330-340.|
|1987||Carter DR, Orr TE, Fyhrie DP, Schurmant DJ. Influences of mechanical stress on prenatal and postnatal skeletal development. Clin Orthop Relat Res. June 1987;219:237-250.|
|1941||Biot MA. General theory of three‐dimensional consolidation. J Appl Phys. February 1941;12(2):155-164.|
|1992||Guilak F. Cell-Matrix Interactions and Metabolic Changes in Articular Cartilage Under Compression [PhD thesis]. Columbia University; 1992.|
|1987||Mak AF, Lai WM, Mow VC. Biphasic indentation of articular cartilage, I: theoretical analysis. J Biomech. 1987;20(7):703-714.|
|1988||Carter DR, Wong M. Mechanical stresses and endochondral ossification in the chondroepiphysis. J Orthop Res. January 1988;6(1):148-154.|
|1991||Lai WM, Hou JS, Mow VC. A triphasic theory for the swelling and deformation behaviors of articular cartilage. J Biomech Eng. August 1991;113(3):245-258.|
|1973||Mori T, Tanaka K. Average stress in matrix and average elastic energy of materials with misfitting inclusions. Acta Metall. May 1973;21(5):571-574.|
|1993||Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science. May 21, 1993;260(5111):1124-1127.|
|1962||McCutchen CW. The frictional properties of animal joints. Wear. January–February 1962;5(1):1-17.|
|1980||Mow VC, Kuei SC, Lai WM, Armstrong CG. Biphasic creep and stress relaxation of articular cartilage in compression: theory and experiments. J Biomech Eng. February 1980;102(1):73-84.|